KEY TAKEAWAYS
- The study aimed to investigate a bio-orthogonal theranostic system for improved PD-L1-targeted imaging and therapy in patients with TNBC.
- Researchers found the bio-orthogonal theranostic system improved PD-L1 imaging and therapy in TNBC.
The combination of programmed cell death ligand-1 (PD-L1) immune checkpoint blockade (ICB) and immunogenic cell death (ICD)-inducing chemotherapy has demonstrated potential in advancing cancer immunotherapy. Nevertheless, patients with triple-negative breast cancer (TNBC) undergoing this treatment often encounter challenges, including systemic toxicity and reduced efficacy, largely due to the immunosuppressive nature of the tumor microenvironment (TME).
Yan Wang and the team aimed to assess the effectiveness of a bio-orthogonal multifunctional theranostic system that integrates PD-L1 targeting with bio-orthogonal click chemistry.
They performed an inclusive analysis of PD-L1-targeted theranostic systems developed using anti-PD-L1 peptide (APP) conjugated with a bio-orthogonal click chemistry group. Initially, patients with TNBC were treated with azide-modified sugar to introduce azide groups onto tumor cell surfaces through metabolic glycoengineering. A PD-L1-targeted probe was then utilized to assess the PD-L1 status of TNBC via magnetic resonance and near-infrared fluorescence imaging.
Subsequently, an acidic pH-responsive prodrug was employed to enhance tumor accumulation through bio-orthogonal click chemistry, facilitating PD-L1-targeted immune checkpoint blockade, pH-responsive doxorubicin release, and induction of pyroptosis-mediated ICD. This combined approach effectively reversed the immune-tolerant TME and triggered strong tumor-specific immune responses, leading to notable tumor progression inhibition.
The study concluded that the bio-orthogonal multifunctional theranostic system, integrating bio-orthogonal click chemistry with PD-L1 targeting, shows significant promise for enhancing both imaging and therapeutic interventions in TNBC.
This study was funded by the National Natural Science Foundation of China (82071870, 92159203, 81901870), the Sponsored Program of Shanghai Science and Technology Committee (No. 21S31905000), the Shanghai Rising-Star Program (22QA1406000) and Natural Science Foundation of Shanghai (21ZR1441600).
Source: https://pubmed.ncbi.nlm.nih.gov/39090622/
Wang Y, Chen Y, Ji DK, et al. (2024). “Bio-orthogonal click chemistry strategy for PD-L1-targeted imaging and pyroptosis-mediated chemo-immunotherapy of triple-negative breast cancer.” J Nanobiotechnology. 2024 Aug 1;22(1):461. doi: 10.1186/s12951-024-02727-7. PMID: 39090622; PMCID: PMC11293135.
